Fungicidal preparations



United States Patent FUNGICIDAL PREPARATIONS No Drawing. Application March 26, 1956 Serial No. 573,649

7 Claims. (Cl. 167-58) This invention relates to the control of fungus growth and particularly to improved fungicidal agents adapted to inhibit such growth. v

; It is a primary object of the invention to provide compositions of high fungicidal activity which are suitable for use on the human body and particularly for the control of fungus growth on the skin.

I have found that certain phenylmercapto compounds of thetype hereinafter described are useful as the active ingredient in fungicidal compositions containing mixtures of such compounds with suitable diluents. Forexample, these compounds have been found to be excellent inhibitors of such pathological fungi as:

Candida albicans Trichophyton mentagrophytes Trichophyton gypseum Trichrophyton rubrum Trichophyton purpureum Trichophyton crateriforme Trichophyton schoenleini Trichophyton tonsurans Epidermophyton floccosum Blastomyces dermatitidis Microsporum canis Microsporum gypseum Microsporum fulvum MicrosporumJ audouini In general, I employ as the active ingredient in my fungicidal compositions a compound having the general formula:

stantially innocuous to the various materials to which Phenylmercaptoethanol they are applied, when used in the amounts necessary for inhibition of fungus growth. In general, compositions containing between 2% and 10% of the phenylmercaptoaliphatic compound are preferred. Where skin areas have become tender due to fungus infections, it is desirable to use concentrations in such treatment not higher than 15%. Concentrations higher than 15%, while effective in fungus growth inhibition, have a tendency to be too harsh for application to such tender raw areas.

The effectiveness of these compounds as inhibitors of ice the fungi hereinbefore mentioned has been demonstrated by extensive in vitro tests. For example, tests were made upon the fungus Candida albicans which is a disease-producing organism causing both superficial and systemic infections characterized by a high order of resistance to chemotherapy. The lack of sensitivity of Candida albicans to the inhibiting and fungicidal action of most antifungal agents has long been recognized. It can be taken as a general rule, therefore, with but few exceptions that any chemical agent active against Candida albicans will show a similar or greater activity against other pathogenic fungi.

Because Candida albicans grows well and quickly on artificial media, it lends itself particularly to the following eifectiveness test. It is to be understood, however, that the test procedure is substantially the same when applied to other fungi.

TEST METHOD Small volumes (.16-.25 cc.) of acetone solutions of varying concentrations of the fungicidal compound are added to a series of tubes containing sterile, melted Sabourauds agar. The tubes are first shaken to disperse the compound and are then cooled in an inclined position to solidify the agar. In general, concentrations of 25, 12.5, 6.2, 3.1, 1.5, .7, .3 and .15 milligrams of the fungicidal compound per 20 cc. of media are obtained. The surface of the treated agar in each tube is then streaked with a one millimeter loop of a suspension prepared by suspending a 2448 hour Sabourauds agar culture of Candida albicans (or other fungus) in 2 cc. of sterile distilled water. The innoculated tubes are stored at room temperature for 48 hours and then checked for evidence of growth. The lowest concentration of acid which completely prevents growth measures the activity of the compound under test.

In the case of other fungi the test procedure is the same as described above, except that the aging period should be continued for at least 10 days. I

In thefollowing table the activity or effectiveness of representative compounds of the invention against various pathogenic fungi is given. The activity in each instance is represented in milligrams per 20 cc. of agar required to prevent growth, using the test method outlined above.

Table I Trichophyton aypseum Trickevphyla n rubrum Microaporum cant:

Microsporum 0111 Candida Phenylmercaptoacetic acid methyl ester-.-"

Phenylmercaptoacetic acid ethyl ester- Twelve and a half milligrams in 20 cc. of agar represents a concentration in the range of .06% by weight. Although concentrations less than those indicated in Table I also tend to exert an inhibitory influence, the inhibition may be incomplete in the particular environment.

The preferred method by which I inhibit fungus growth is by utilizing a dusting powder in which the fungicidal agent is mixed with finely powdered diluent dusts such I as talc, corn starch, rice, starch, kaolin, precipitated chalk, zinc oxide, zinc stearate, magnesium oxide and the like. Any generally non-toxic inert powder may be utilized as a diluent.

The following examples of fungus inhibitory dusts are given by way of illustration.

EXAMPLE 1 Percent Phenylmercaptoethanol .3 to 10 Talc 99.7 to 90 EXAMPLE 3 Percent Phenylmercaptopropanol l Talc Y Y 6}) Starch- Kaolin Y e 10 I EXAMPLE 4 I fhenylmercaptoethanol 10 Talc 7 50 Starch 1 20 Zinc oxide H or a 20 EXAMPLE 5 Phenylmercaptobutanol 2 Boric acid v 35 Zinc stearate 3 Exsiccated alum 1 Starch 1'0 Talc 78 EXAMPLE 6 Phnyl'mercaptoacetic acid methyl ester 45 Talc 55 Phenylmercaptoacetic acid ethyl ester .2 to 15 EXAMPLE 8 Phenylme'rcaptoethanol .2 to 15 Petrolatum 99.8 to 85 EXAMPLE 9 Phenylmercaptoacetic acid methyl ester 50 Petrolatum 50 I The following are examples of useful fungus-inhibitory solutions:

EXAMPLE 10 Percent Acetone Phenylmercaptoacetic acid ethyl ester .5

' EXAMPLE 11 95% Ethyl alcohol 98 Phenylmercaptoe'thanol 2 EXAMPLE 12 Acetone H i e 9S Phenylmercaptoacetic acid methyl ester 5 EXAMPLE 13 Alpha-n propylphenylmercaptoacetic acid methyl I Acetone 99.5

I EXAMPLE 14 Alpha-butylph'enylmercaptoacetic acid methyl 'ester -1. v 2 95% ethyl alcohol e 98 The following is an example of a non-drying fungusii'iliibitory solution:

EXAMPLE 15 Glycerine 90 Phenylmercaptoacetic acid ethyl ester 10 In some instances it is desirable to employ conventional propellent liquids as the carrier. By propellent liquids I refer to gaseous carriers which have been liquefied under pressure and have admixed therewith a solid or liquid agent. Such carriers, when released from confinement through a small orifice in the form of a fine spray, carry the liquid or solid agent with them, thereby serving as a propellant. The preferred materials for this purpose arethe fluorinated hydrocarbon propellants, particularly derivatives of methane and ethane.

The following are examples of suitable propellent mixtures or solutions:

EXAMPLE 16 Percent Phenylme'rcaptoethanol 5 lsopropanol 5 Trichloro monofiuoromethane 45 Dichloro difluoromethane 45 EXAMPLE 17 Dichloro tetrafiuoroethane 93 Isopropanol 5 Phenylmercaptoacetic acid ethyl ester 2 EXAMPLE 18 Dimethyl ester 85 Ethyl alcohol 5 Alpha-phenylmercaptopropanol 10 EXAMPLE 19 Carbon dioxide 92 Alpha-phenylmercaptobutanol -5 8 EXAMPLE 20 Ethyl chloride Phenylmercaptoacetic acid methyl ester 5 The solutions of Examples 16 to 20 are all propellent mixtures which are applied under pressure from a conventional bomb type can.

Although it is usually preferable to employ between about 2 and 10% of the fungicidal agent in compositions intended for use on human skin, in some instances concentrations as high as 20% of the agent based on the total weight of the non-volatile constituents of the composition may be employed without harm. When the methyl ester of phenylmercaptoacetic acid is employed as the agent, concentrations as high as 50% may be used. Moreover, when applying the fungicidal agents of the invention to surfaces other than the skin, they may fre quently be applied in higher concentrations to advantage.

I claim:

1. The method of inhibiting the growth of pathogenic, parasitic fungus which comprises contacting a medium subject to said growth with a compound having the general formula:

in which Ar is a phenyl group; Z is a member selected from the group consisting of hydrogen and an alkyl radiv cal containing from 1 to 5 carbon atoms; n is a numeral varying from 0 to 4; and X is a member selected from the group consisting of the hydroxy radical and a carbalkoxy radical in which the alkyl group contains from -1 to 3 carbon atoms. 1

2. The method of claim 1 in which the compound is phenylme'rcaptoa'cetic acid methyl ester.

3. The method of inhibiting the growth of pathogenic, parasitic fungus which comprises contacting the growth with a composition containing from 2 to 10% by weight of a compound having the general "formula:

in which Ar is a phenyl group; Z is a member selected from the group consisting of hydrogen and an alkyl radical containing from 1 to 5 carbon atoms; 11 is a numeral varying from 0 to 4; X is a member selected from the group consisting of the hydroxy radical and a carbalkoxy 5 radical in which the alkyl group contains from 1 t0 3 carbon atoms; and from 90 to 98% of a carrier therefor.

4. The method of claim 3 in which the carrier is a non-toxic powdered diluent.

5. The method of claim 3 in which the carrier is a 10 2396513 non-toxic liquid diluent.

6. The method of claim 3 in which the carrier is a nontoxic propellent liquid.

References Cited in the file of this patent UNITED STATES PATENTS Jacobson May 7, 1946 Jones Mar. 12, 1946 Elson Oct. 21, 1952 

3. THE METHOD OF INHIBITING THE GROWTH OF PATHOGENIC, PARASITIC FUNGUS WHICH COMPRISES CONTRACTING THE GROWTH WITH A COMPOSITION CONTAINING FROM 2 TO 10% BY WEIGHT OF A COMPOUND HAVING THE GENERAL FORMULA: 